This proposal has as its primary goal addressing practical questions of clinical importance in order to facilitate the transition of penicillin skin testing from investigational studies to disseminated judicious use by practicing physicians. In addition, more fundamental questions with broader implications for the general problem of penicillin allergy will be explored. This project involves institution of a longitudinal clinical study of multiple aspects of penicillin allergy in a well-characterized venereal disease clinical population. The focus of the study is to define more precisely the clinical indications for the use of penicillin skin tests. Specifically, the clinical utility of routine skin testing on patients without prior adverse reactions to penicillin will be investigated; the cost of such an undertaking will be compared with the expected benefits in terms of reduction of acute morbidity and mortality from penicillin allergic reactions. Additional questions to be addressed by this research effort include (a) determination of optimal skin test reagents, specifically concerning the "minor determinant" penicillin mixture with the use of benzylpenicillin alone; (b) further assessment of the risks and benefits of treating history-positive but currently skin test-negative patients; (c) evaluation of the effect of prior IgE-mediated penicillin reactions on subsequent risks of non-IgE-mediated (late occuring) reactions, and vice versa; (d) assessment of serological distinctions in terms of penicilloyl IgG and IgE antibodies, both pre- and post-treatment among pencillin reactors as compared with controls; (e) establishing the natural history of IgE-mediated penicillin allergies in terms of disappearance of positive penicillin skin tests and pencilloyl RAST assays over times and (f) comparison of results of penicilloyl RAST analysis with direct skin tests with penicilloyl polylysine.